Concurrent activation of c-myc and inactivation of bcl-2 by chromosomal translocation in a lymphoblastic lymphoma cell line.
We have characterized a chromosomal translocation in a cell line (SU-DUL5) established from a patient with lymphoblastic lymphoma in which the c-myc gene on chromosome 8 was juxtaposed to a t(14;18). Cytogenetic analysis of this cell line showed 14q+, 18q-, and 8p+q+ marker chromosomes in the absence of t(14;18). Genomic Southern blot analysis showed juxtaposition of the immunoglobulin heavy chain joining region (JH) with chromosome 18 near the minor breakpoint cluster region (mcr) of the bcl-2 gene. There was also a rearranged c-myc gene detectable with a 5' c-myc probe. Molecular cloning studies showed that the c-myc gene was joined to chromosome 18 DNA. Nucleotide sequence analysis of cloned breakpoint DNA revealed that the crossover between chromosomes 8 and 18 occurred at the 3' end of the bcl-2 gene resulting in replacement of the bcl-2 gene on the 14q+ chromosome with the c-myc gene. As a result of this translocation the SU-DUL5 cell line contains no detectable bcl-2 mRNA or protein but has abundant levels of c-myc mRNA. Our data suggest that bcl-2 inactivation occurred simultaneously with c-myc translocation in a B cell lymphoblastic lymphoma.
Kiem
H P
HP
Division of Hematology, Stanford University School of Medicine, California 94305.
Nourse
J
J
Saltman
D L
DL
Blume
K G
KG
Cleary
M L
ML
D000328:Adult; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002898:Chromosomes, Human, Pair 8; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger